Inhibition of cytochrome P450 enzymes by cirsimaritin and its properties invitro

  • Arch Biochem Biophys. 2026 Aug:782:110834. doi: 10.1016/j.abb.2026.110834.
Xiangcheng Li  1 ,  Yawei Shi  2 ,  Dandan Liu  3
Affiliations
  • 1. Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
  • 2. Shanghai Zhongqiao Vocational and Technical University, Shanghai, 201514, China.
  • 3. Pharmacy Department, Ganzhou Hospital-Nanfang Hospital, Southern Medical University (Ganzhou People's Hospital), Ganzhou, 341000, China. Electronic address: [email protected].
PMID: 42061548 DOI: 10.1016/j.abb.2026.110834
Abstract

Background: The flavonoid cirsimaritin has pharmacological activities that potentially modulate inflammatory responses, tumor progression, and glucolipid metabolism. However, its influence on Cytochrome P450 (P450) enzyme activity remains unexplored.

Objective: This study examines the influence of cirsimaritin on P450 activity, aiming to offer further guidance for its clinical use.

Methods: The effect of cirsimaritin on key P450 isoform activities was investigated in pooled human liver microsomes (HLMs) using specific substrates. The half-maximal inhibitory concentrations (IC50) for the inhibition of P450 isoforms were determined using different doses of cirsimaritin. The type of inhibition was further assessed using different concentrations of substrates. Furthermore, time-dependent experiments were performed to obtain the corresponding kinetic parameters.

Results: Cirsimaritin inhibited the activity of CYP1A2, CYP3A4, and CYP2C9 with significant concentration-dependent changes, and the IC50 values were 18.4 ± 2.7, 15.3 ± 2.6, and 9.67 ± 1.9 μM, respectively. Cirsimaritin exhibited non-competitive inhibition of CYP3A4, with the inhibition constant (Ki) value of 7.81 ± 0.79 μM. Cirsimaritin was a competitive inhibitor of CYP1A2 and CYP2C9, with Ki values of 9.33 ± 0.65 μM and 4.81 ± 0.51 μM, respectively. In addition, the inhibitory effect of cirsimaritin on CYP3A4 was further found to be time-dependent, with the maximal rate of enzyme inactivation (kinact) value of 0.035 ± 0.005 min-1 and the concentration of cirsimaritin at half of the kinact (KI) value of 6.52 ± 0.81 μM.

Conclusions: The observed inhibition of CYP1A2, CYP3A4, and CYP2C9 by cirsimaritin indicates its potential to cause herb-drug interactions with drugs metabolized by these isoforms. Further in vivo studies are needed to confirm such interactions.

Keywords
Cirsimaritin; Competitive inhibitor; Cytochrome P450; Human liver microsomes; Time-dependent inhibition.
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